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In muscle cells order 150 mg avapro amex blood glucose journal template, as in other cells best 300mg avapro diabetes medications in the pipeline, phorylation pathway provides the greatest amount of en- this energy ultimately comes from the universal high-en- ergy, it cannot be used if the oxygen supply is insufficient; ergy compound, ATP. Glucose is the preferred Muscle Cells Obtain ATP From Several Sources fuel for skeletal muscle contraction at higher levels of exer- Although ATP is the immediate fuel for the contraction cise. At maximal work levels, almost all the energy used is process, its concentration in the muscle cell is never high derived from glucose produced by glycogen breakdown in enough to sustain a long series of contractions. Most of the muscle tissue and from bloodborne glucose from dietary immediate energy supply is held in an “energy pool” of the sources. Glycogen breakdown increases rapidly during the compound creatine phosphate or phosphocreatine (PCr), first tens of seconds of vigorous exercise. After a mole- and the subsequent entry of glucose into the glycolytic cule of ATP has been split and yielded its energy, the re- pathway, is catalyzed by the enzyme phosphorylase a. The creatine phosphate pool is restored by action is, in turn, stimulated by the increased Ca con- ATP from the various cellular metabolic pathways. These centration and metabolite (especially AMP) levels associ- reactions (of which the last two are the reverse of each ated with muscle contraction. Increased levels of circulat- other) can be summarized as follows: ing epinephrine (associated with exercise), acting through cAMP, also increase glycogen breakdown. Sustained exer- ATP → ADP Pi (Energy for contraction) (1) cise can lead to substantial depletion of glycogen stores, which can restrict further muscle activity. ADP PCr → ATP Cr (Rephosphorylation of ATP) (2) Other Important Energy Sources. At lower exercise lev- ATP Cr → ADP PCr (Restoration of PCr) (3) els (i. Fat, the tration of PCr can fall to very low levels before the ATP major energy store in the body, is mobilized from adipose concentration shows a significant decline. It has been tissue to provide metabolic fuel in the form of free fatty shown experimentally that when 90% of PCr has been acids. This process is slower than the liberation of glucose CHAPTER 8 Contractile Properties of Muscle Cells 149 Energy produced Energy used Blood Muscle cell Creatine ADP phosphate 2 PCr ATP restored replenished A Actomyosin ATPase (contraction) 1 Creatine ATP B SR Ca2+ pump (relaxation) Glycogen C Other metabolic functions 36 (ion pumping, etc. The scheme shown here is typical for all types of of ATP for the actomyosin ATPase of the crossbridges. Energy muscle, although there are specific quantitative and qualitative sources are numbered in order of their proximity to the actual re- variations. Moderate activity, with brief rest Continue With an Inadequate Oxygen Supply periods, favors the consumption of fat as muscle fuel. Glycolytic (anaerobic) metabolism can provide energy Complete combustion of fat yields less ATP per mole of for sudden, rapid, and forceful contractions of some oxygen consumed than for glucose, but its high energy muscles. In such cases, the ready availability of gly- storage capacity (the equivalent of 138 moles of ATP per colytic ATP compensates for the relatively low yield of mole of a typical fatty acid) makes it an ideal energy store. The depletion of body fat reserves is almost never a limit- In most muscles, especially under conditions of rest or ing factor in muscle activity. However, protein is used by products of glycolysis) to supply the energy needs of the muscles for fuel mainly during dieting and starvation or contractile system. Under such conditions, proteins are several physiological mechanisms come into play to in- broken down into amino acids that provide energy for con- crease the blood supply (and, thus, the oxygen) to the traction and that can be resynthesized into glucose to meet working muscle. The gly- ing energy for contraction and the recycling of metabolites colytic pathway can continue to operate because the ex- (e. In addition to its oxygen- and formation of lactic acid, by preventing a buildup of pyru- carbon dioxide-carrying functions, the enhanced blood vic acid, also allows for the restoration of the enzyme supply to exercising muscle provides for a rapid exchange cofactor NAD , needed for a critical step in the gly- of essential metabolic materials and the removal of heat. Thus, ATP can continue to be produced under Those muscles adapted for mostly aerobic metabolism anaerobic conditions. This The accumulation of lactic acid is the largest contributor iron-containing molecule, essentially a monomeric form of (more than 60%) to oxygen deficit, which allows short-term the blood protein hemoglobin (see Chapter 11), gives aer- anaerobic metabolism to take place despite a relative lack of obic muscles their characteristic red color. Other depleted muscle oxygen stores have a smaller gen storage capacity of myoglobin is quite low, and it does capacity but can still participate in oxygen deficit.

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Volar plate fractures are quite (fatigue fractures) or in the elderly with osteoporosis or common and are seen at the volar aspect of the base of other underlying disease (insufficiency fractures) purchase avapro 150 mg on line diabetic lunch recipes. These may be impossible to identify Conventional imaging signs may be subtle or non-exis- on PA radiographs but are usually evident on oblique or tent purchase 150mg avapro mastercard diabetes type 2 cure. Others will have no joints may be seen in association with volar plate injuries; findings on conventional imaging and the presence of the a dislocation may have been reduced prior to imaging. This is often accompanied by a fracture at the site the hip are not uncommon, particularly in athletes. The of avulsion and may require stress views for evaluation most common of these include avulsion fractures from when the injury is purely ligamentous. If the adductor the site of origin of the hamstring muscles (the ischial aponeurosis is entrapped within the joint (Stenner lesion), tuberosity), avulsions from the straight or reflected heads then surgery may be necessary. Ultrasound and MRI of the rectus femoris (seen at the anterior inferior iliac have been advocated for the diagnosis spine or in the supra-acetabular region), and avulsions of the lesser trochanter. Dislocations of the hip are most commonly posterior Specific Sites - Lower Extremity and are frequently associated with fractures of the poste- rior wall of the acetabulum. Osteochondral or shear frac- Hip tures of the femoral head (Pipkin fractures) occur where the femoral head strikes the acetabulum at the time of Fractures of the femoral neck may be displaced, with re- posterior dislocation. In a posterior dislocation, the sultant shortening and external rotation of the lower ex- hip is displaced posteriorly and often slightly superiorly; tremity. Although these are readily diagnosed by conven- the thigh is held in adduction. Much less common are an- tional imaging, at times there is an apparent radiolucen- terior dislocations of the hip, in which the femoral head cy in the femoral neck, suggesting that the fracture is is seen in a medial and inferior position; the thigh is held pathologic. The area of lucency is due to rotation of the fracture frag- Knee ments. When femoral-neck fractures are impacted, diag- nostic problems increase. The position of the hip is usu- Routine imaging includes at least two views, AP and lat- ally in valgus and these fractures may be recognized as eral. Tangential views of the patella and tunnel views may bands of density extending across the femoral neck or by be used to supplement these, particularly when joint ef- a “squared-off ” contour to the head-neck junction along fusions are demonstrable. Patients with im- be helpful in detecting fractures of the tibial plateau. If a lipohemarthrosis is demonstrable on hori- tertrochanteric region; the lesser trochanter may represent zon-beam images, this is presumptive evidence for an in- a separate bony fragment in these cases. In these cases, CT is often the most tures of the greater trochanter should raise the possibility expeditious way to demonstrate these fractures. In patients with CT may not be able to detect other intra-articular abnor- conventional images indicating an avulsion of the greater malities. For this reason, MRI may be even more useful trochanter, MRI should be preformed in order to evaluate as it can detect ligamentous injuries, meniscal tears and the intertrochanteric region for incomplete fracture. Osteochondral injuries of the femoral condyles displacement of the medial fragment. Avulsion fractures at process of the calcaneus occur and must be distinguished the insertion of the posterior cruciate ligament are often from normal variants in this location. Knowledge of the in- missed on conventional imaging and diagnosis often fol- sertion point of the posterior cruciate ligament in this lo- lows MRI performed for persistent ankle pain. This fracture, which can be usually readily demonstrable on tangential views of the demonstrated on conventional imaging, has an extremely calcaneus or on CT. When this fracture is identified, MRI will clearly the calcaneus and navicular. In adolescent athletes, epiphyseal separations are cult to see on conventional imaging and may require CT more common than ligamentous injuries. Asymmetry in the width of the growth plate or small fracture fragments on The Forefoot the metaphyseal side of the growth plate should be suffi- cient to establish the diagnosis in most cases. MR may be The Lisfranc fracture-dislocation of the tarso-metatarsal a valuable technique when the nature of the injury is in joints is a frequent injury.

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Through fre- Smooth muscle fibers on either side of the quent blinking discount 150 mg avapro free shipping diabetes symptoms in toddlers, the eyelid helps keep the pupil cause it to contract or dilate buy cheap avapro 150mg on line diabetes type 2 reversal diet, there- eye moist, preventing irritation. The by automatically regulating the amount of lacrimal glands, which lie in the upper out- light that enters the eye. In bright light er side of the eye behind the eyelid, secrete the pupil contracts to reduce the amount tears to keep the eyeball moist and help of light admitted. In front of the eye lies a transparent Directly behind the iris is a space called curved structure called the cornea, which the posterior chamber. Contained in the admits light and protects the inner eye posterior chamber is a structure called the from foreign particles and organisms. The vessels, it is richly supplied with nerve aqueous humor escapes from the posteri- cells. Connected to the cornea and com- or chamber through the pupil into a space pletely covering the eyeball except for the lying between the iris and cornea called part covered by the cornea is a fibrous the anterior chamber, which lies between membrane called the sclera. The aqueous forms the white part of the eye and has humor then drains from the eye into the primary function of supporting and lymph channels and into the venous sys- protecting the eye and maintaining eye tem through a sievelike structure called shape. Lining the exposed area of the scle- the canal of Schlemm (trabecular network), ra and inner eyelid is a sensitive mem- which is located at the junction of the iris brane called the conjunctiva. The balance between the underneath the sclera and also surround- amount of aqueous humor produced and 123 124 CHAPTER 4 CONDITIONS OF THE EYE AND BLINDNESS Muscle Chorid Retina Conjunctiva Ciliary muscle Iris Aqueous humor Fovea Cornea (Macular area) Pupil Optic nerve Lens Optic disc Vitreous Anterior chamber humor Posterior chamber Canal of Schlemm Sclera Figure 4–1 The Eye. This space is filled with a jelly- cornea and a structure located directly like, translucent substance called the behind the iris called the lens. The lens is vitreous humor, which helps to maintain a small transparent disk enclosed in a the form and shape of the eyeball. Attachments around At the very back of the eye is the inner- the circumference of the lens, called ciliary most coat of the eye, the retina. The reti- muscles, automatically contract or ex- na contains two layers, a pigmented layer pand, changing the shape of the lens from that is fixed to the choroid and an inner fat to thin or vice versa in response to the layer that contains special light-sensitive proximity or distance of an object being cells called rods and cones. The changing shape of the lens Rods are involved with detecting light permits the eye to focus for near or far and dark as well as shape and movement vision, a process called accommodation. Rods contain iary muscles relax, thinning and flatten- a derivative of vitamin A, rhodopsin, a ing the lens. To focus on objects close by, highly light-sensitive substance that breaks Measuring Vision 125 down rapidly when exposed to light. This of best vision and to measure the need for chemical process causes a reaction that corrective lenses. A standard test of visu- activates the rods so that the eye adjusts, al acuity is the Snellen test. Lines are Cones are involved primarily in daylight identified according to the distance from and color vision as well as in the percep- which they can be read by individuals tion of sharp visual detail. For example, cones are located in a spot on the retina individuals with normal visual acuity can called the macula. The macula is the area read the top line of the chart at 200 feet of clearest central vision. When taking macula, the fovea, contains no rods and is the Snellen test, individuals view the the area where vision is clearest in good Snellen chart at the equivalent of 20 feet light. This are expressed as a fraction, the numerator area is sometimes called the blind spot denoting the equivalent distance from the because it does not contain light-sensitive chart at which the individual being test- cells. Light rays pass through the cornea, ed views the chart (20 feet) and the enter the pupil, pass through the lens, and denominator denoting the distance from register on the retina. Sensory cells of the the chart at which a person with normal retina receive light stimuli and convert vision would be able to read the same line. These elec- Consequently, a visual acuity of 20/100 trical impulses are then transmitted to the means that the individual being tested can optic nerve, which carries them to the see at 20 feet what a person with normal occipital lobe of the brain, where they are visual acuity could see at 100 feet, indicat- interpreted. On the other hand, a result of nerves from each eye combine at the base 20/10 would indicate that the individual of the brain just in front of the brain stem being tested has better-than-normal visu- to form the optic chiasm.

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There is glycogen stored in the liver discount avapro 150 mg online blood glucose hypoglycemia, the more important source of also significant gluconeogenesis in liver from the glycerol blood glucose during the first days of a fast is gluconeoge- released from triglyceride by lipolysis buy 150 mg avapro diabetes cat. In prolonged fast- nesis in the liver and, to some extent, in the kidneys. Amino acids derived from tissue protein are the main rived from triglyceride glycerol. Fasting results in protein breakdown in the Within a few hours of the start of a fast, the increased skeletal muscle and accelerated release of amino acids into delivery to and oxidation of fatty acids in the liver results in the bloodstream. Protein breakdown and protein accretion the production of the ketone bodies. As a result of these in adult humans are regulated by two opposing hormones, events in the liver, a gradual rise in ketone bodies occurs in insulin and glucocorticoids. During fasting, insulin secre- the blood as a fast continues over many days (Fig. As proteins are broken down, the CNS during the later stages of fasting. Two products acids released into the blood by the skeletal muscle are ex- resulting from the breakdown of fatty acids, acetyl CoA tracted from the blood at an accelerated rate by the liver and citrate, inhibit glycolysis. The amino acids then undergo metabolic use of glucose from the blood is reduced. The newly synthesized glucose is then delivered tion to fasting is to provide the body with glucose pro- to the bloodstream. From that point on, the in this process by maintaining gene expression and, there- body uses mainly fat for energy metabolism, and it can fore, the intracellular concentrations of many of the en- survive until the fat depots are exhausted. Glucocorticoids zymes needed to carry out gluconeogenesis in the liver and do not trigger the metabolic adaptations to fasting but kidneys. For example, glucocorticoids maintain the only provide the metabolic machinery necessary for the amounts of transaminases, pyruvate carboxylase, phospho- adaptations to occur. When present in excessive amounts, needed to carry out gluconeogenesis at an accelerated rate. Cushing’s disease is the name of amounts of these enzymes in the liver are greatly reduced. Cushing’s disease CHAPTER 34 The Adrenal Gland 619 may be ACTH-dependent or ACTH-independent. One plasma membrane phospholipids by the hydrolytic action type of ACTH-dependent syndrome (actually called Cush- of phospholipase A2. Glucocorticoids stimulate the syn- ing’s disease) is caused by a corticotroph adenoma, which thesis of a family of proteins called lipocortins in their tar- secretes excessive ACTH and stimulates the adrenal cortex get cells. Lipocortins inhibit the activity of phospholipase to produce large amounts of cortisol. ACTH-independent A2, reducing the amount of arachidonic acid available for Cushing’s syndrome is usually due toa result of an adreno- conversion to prostaglandins and leukotrienes. Whatever the cause, prolonged exposure of the body to Effects on the Immune System. Glucocorticoids have large amounts of glucocorticoids causes the breakdown of little influence on the human immune system under normal skeletal muscle protein, increased glucose production by physiological conditions. When administered in large the liver, and mobilization of lipid from the fat depots. De- doses over a prolonged period, however, they can suppress spite the increased mobilization of lipid, there is also an ab- antibody formation and interfere with cell-mediated immu- normal deposition of fat in the abdominal region, between nity. Glucocorticoid therapy, therefore, is used to suppress the shoulders, and in the face. The increased mobilization the rejection of surgically transplanted organs and tissues. The underutilization of glucose concentrations of glucocorticoids, decreasing the number by skeletal muscle, coupled with increased glucose produc- of circulating lymphocytes. The destruction of immature T tion by the liver, results in hyperglycemia, which, in turn, and B cells by glucocorticoids also causes some reduction in stimulates the pancreas to secrete insulin. Glucocorticoids are required for the normal responses of vas- Evidence also indicates that excessive glucocorticoids de- cular smooth muscle to the vasoconstrictor action of norep- crease the affinity of insulin receptors for insulin. NE is much less active on vascular smooth muscle result is that the individual becomes insensitive or resistant in the absence of glucocorticoids and is another example of to the action of insulin and little glucose is removed from the permissive action of glucocorticoids.

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